Aging‐Associated Changes in Murine Intestinal Immunoglobulin A and M Secretions

Abstract

The aging effect on the quantity of intestinal IgA and IgM class-specific immunoglobulins secreted and the quality of intraluminal intestinal IgA was studied in 5- to 6-month-old and 24- to 28-month-old male BALB/c mice. The level of IgA increased in the intestinal juice from the aged mice, while the IgM level remained unchanged. These alterations were similar to those found in serum, but the effect of age on serum IgA was profound, almost a threefold increase, in contrast to an increase of just under 35% in intestinal secretions. The ratio of dimeric to total IgA in the small intestine decreased in the older mice, though that of serum was unchanged. In contrast, the total amounts of dimeric IgA in the small intestinal lavage fluid did not change between the two age groups, while the dimeric IgA in serum in older mice were 4.5 times as high as those of young mice. The binding of purified intestinal dimeric IgA to antigens from normal habitant enteric bacteria (gamma streptococci and Enterobacter agglomerans) declined in the old mice. In the immunochemical studies, using SDS-PAGE and isoelectric focusing, the purified intestinal IgA from the young and old mice showed no major differences. Thus, the findings in aged small intestinal perfusates that the increased content of intraluminal IgA is due to an increased monomeric IgA, but not to a reduced dimeric IgA, which remains unchanged, and that the binding capacity of the dimeric IgA to the bacterial antigens is diminished, suggest that the level of the natural secretory IgA antibody is decreased. These altered quantitative and functional features of intraluminal intestinal IgA observed in the aged mice appear to be due to the complex heterogeneous effects of senescence on gut-associated lymphoid tissues, and may contribute to age-related impairment in gut humoral immune function.

The intranasal adjuvant Endocine™ enhances both systemic and mucosal immune responses in aged mice immunized with influenza antigen

“…3c). This is not completely unexpected, as previous analyses have shown a similar difference in IgA levels between young and older mice in gut tissue [35, 36]. Interestingly, even though the frequency of local mucosal B cells in gut tissue is reduced in elderly mice, the synthesis and secretion of immunoglobulins was shown to be higher in older mice compared to young mice [35].…”

Aging impacts isolated lymphoid follicle development and function

“…Some studies have reported increases or no change in the serum IgA levels in old animals and humans [26-29]. A few studies also reported the absence of age-related differences in the amounts of nonspecific immunoglobulins secreted into the intestinal lumen in vivo or into the medium by cultured duodenal biopsies [28-31], while other studies observed that the production of antigen-specific IgA is diminished with aging [14,32,33]. …”

Aging and immunoglobulin isotype patterns in oral tolerance

“…There is a depression in early signal transduction as well as a reduction in calcium fluxes (45)(46)(47)(48) in activated B and T lymphocytes in old animals. The levels of dimeric IgA produced in gut lamina propria as well as the number of CD4 + T cells in Peyers patches are significantly reduced in old animals (49,50).…”